Streptococcal M protein isolated with non-ionic detergent has been purified and characterized both chemically and physically. Selected M proteins from cross-reactive and non-cross-reactive types will be compared by chromatographic peptide mapping procedures to determine if common peptides exist between these M types. Selective enzymatic and chemical cleavage of the anti-phagocytic and type-specific molecules will be performed with the isolation of biologically and immunologically active peptides. Isolated peptides will be used in radioactive competitive inhibition experiments to determine the antibody response to M protein in both man and rabbits, as well as those peptides involved in cross-production between M types. Isolated cross-protective and anti-phagocytic peptides will be bound to carrier molecules and injected into rabbits to determine if the production of cross-protective and anti-opsonic antibodies can be stimulated. The quaternary structure of M protein will be determined by the use of cross-linking reagents and pulse-chase experiments. Surface radioiodination of streptococcal protoplasts will enable us to determine the type of molecules being transported through the membrane. The anti-phagocytic effect of the M protein will be examined by preparing anti-phagocytic latex or yeast particles by coating them with M protein. By altering specific amino acid residues of the M antigen on these particles, the nature of the anti-phagocytic effect and the residues necessary for binding opsonic antibodies may be resolved. The chemical basis of the antigenic shifts in M protein will be examined by peptide map analysis and competitive inhibition data. Finally, by various in vitro and in vivo analyses, we wish to determine if our preparations of M protein and peptides elicit delayed hypersensitivity reactions as well as any possible cross-reactivity with histocompatibility and cardiac antigens.